1xiv: Difference between revisions
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==Plasmodium falciparum lactate dehydrogenase complexed with 2-({4-chloro-[hydroxy(methoxy)methyl]cyclohexyl}amino)ethane-1,1,2-triol== | ==Plasmodium falciparum lactate dehydrogenase complexed with 2-({4-chloro-[hydroxy(methoxy)methyl]cyclohexyl}amino)ethane-1,1,2-triol== | ||
<StructureSection load='1xiv' size='340' side='right' caption='[[1xiv]], [[Resolution|resolution]] 1.70Å' scene=''> | <StructureSection load='1xiv' size='340' side='right'caption='[[1xiv]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1xiv]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1xiv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XIV FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RB2:2-({4-CHLORO-2-[HYDROXY(METHOXY)METHYL]CYCLOHEXYL}AMINO)ETHANE-1,1,2-TRIOL'>RB2</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RB2:2-({4-CHLORO-2-[HYDROXY(METHOXY)METHYL]CYCLOHEXYL}AMINO)ETHANE-1,1,2-TRIOL'>RB2</scene></td></tr> | |||
<tr | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xiv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xiv OCA], [https://pdbe.org/1xiv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xiv RCSB], [https://www.ebi.ac.uk/pdbsum/1xiv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xiv ProSAT]</span></td></tr> | ||
</table> | |||
<table> | == Function == | ||
[https://www.uniprot.org/uniprot/LDH_PLAFD LDH_PLAFD] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xi/1xiv_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xi/1xiv_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1xiv ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 26: | Line 28: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 1xiv" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Lactate | *[[Lactate dehydrogenase 3D structures|Lactate dehydrogenase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Plasmodium falciparum]] | [[Category: Plasmodium falciparum]] | ||
[[Category: Brady | [[Category: Brady RL]] | ||
[[Category: Cameron | [[Category: Cameron A]] | ||
[[Category: Conners | [[Category: Conners R]] | ||
[[Category: Read | [[Category: Read JA]] | ||
[[Category: Schambach | [[Category: Schambach F]] | ||
[[Category: Sessions | [[Category: Sessions RB]] | ||
Latest revision as of 09:45, 23 August 2023
Plasmodium falciparum lactate dehydrogenase complexed with 2-({4-chloro-[hydroxy(methoxy)methyl]cyclohexyl}amino)ethane-1,1,2-triolPlasmodium falciparum lactate dehydrogenase complexed with 2-({4-chloro-[hydroxy(methoxy)methyl]cyclohexyl}amino)ethane-1,1,2-triol
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedGossypol is a di-sesquiterpene natural-product in the form of a functionalised binaphthyl and is isolated from cotton plants. The compound has long been known to exhibit anti-malarial and other biological activities. Previous studies have indicated that compounds of this type target Plasmodium falciparum lactate dehydrogenase (pfLDH), an essential enzyme for energy generation within the parasite. In this study, we report that simple naphthalene-based compounds, the core of the gossypol structure, exhibit weak inhibition of the parasite lactate dehydrogenase. Crystal structures of the complexes formed by binding of these naphthalene-based compounds to their target enzyme have been used to delineate the molecular features likely to form the gossypol binding site. Two modes of binding are observed: one overlapping the pyruvate but not the co-factor site, the other bridging the binding sites for the co-factor nicontinamide group and pyruvate substrate. This latter site encompasses molecular features unique to Plasmodium forms of LDH and is likely to represent the mode of binding for gossypol derivatives that show selectivity for the parasite enzymes. We also report a substrate analogue that unexpectedly binds within the adenine pocket of the co-factor groove. Although these core pharmacophore-like molecules only exhibit low levels of inhibitory activity, these molecular snapshots provide a rational basis for renewed structure-based development of naphthalene-based compounds as anti-malarial agents. Mapping the binding site for gossypol-like inhibitors of Plasmodium falciparum lactate dehydrogenase.,Conners R, Schambach F, Read J, Cameron A, Sessions RB, Vivas L, Easton A, Croft SL, Brady RL Mol Biochem Parasitol. 2005 Aug;142(2):137-48. Epub 2005 Apr 18. PMID:15978953[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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